Platelet PF-4 Is an Early Marker of Tumor Angiogenesis.

Early tumor detection and treatment is one of the most important determinants of cancer survival. We reported previously, that a ‘platelet angiogenesis proteome’ can detect clinically occult tumors in mice. We now present evidence that changes in platelet content of platelet factor-4 (PF-4) can be a consistent predictor of tumor growth across a spectrum of cancers. The differentially expressed protein was initially identified as a ~8200Da band by SELDI-ToF analysis. The protein band was isolated and positively identified by peptide sequencing and anti-PF-4 SELDI MS as PF-4. The platelet-associated PF-4 appeared to be up-regulated in early growth of human liposarcoma, mammary adenocarcinoma, osteosarcoma and down-regulated in a RIP-Tag model of pancreatic islet cell carcinoma. A 120 day follow-up study of liposarcoma revealed ≥2-fold increases of platelet-associated PF-4 at 19, 30 and 120 days. Concomitantly, only a ~0.5–1 fold decrease in PF-4 in plasma was observed. There were minimal changes in the plasma of animals bearing other human tumor xenografts. We conclude that platelet-associated PF-4, but not its plasma counterpart, may be a promising marker of early tumor growth or tumor recurrence.